Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography (ERAP)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Change in cerebral glucose metabolism
研究概览
简要总结
This single-center, uncontrolled pilot study aims to evaluate the efficacy, safety, and tolerability of six months of intermittently dosed oral rapamycin (sirolimus) in subjects with early-stage Alzheimer's disease.
Fifteen participants will be recruited. Following a set of baseline measurements, all participants will receive a weekly oral dose of 7 mg rapamycin for six months. Participants will be continuously monitored for safety and side effects. At the termination of the treatment, follow-up measurements will be taken.
The primary endpoint will be change in cerebral glucose metabolism, measured using 18F labeled fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET).
In addition to the registered outcome measures this pilot trial will explore the feasibility of acquiring data on the effect of sirolimus treatment on age-related tissue changes in the body using a variety of imaging modalities, such as bone mineral density assessed using quantitative computed tomography, retinal structures assessed using optical coherence tomography, periodontal tissue assessed using MRI and FDG-PET, cardiac function assessed using MRI, vessel wall in large arteries using MRI and [18F]FDG PET.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of mild cognitive impairment (MCI), or dementia of Alzheimer's type
- •Amyloid positivity established with either amyloid positron emission tomography or cerebrospinal fluid analysis.
- •For subjects with dementia, the disease should be in an early stage, operationalized as:
- •Stage 4 (Mild dementia) or lower, according to the National Institute on Aging - Alzheimer's Association 2018 clinical staging criteria, AND
- •Clinical Dementia Rating Scale (CDR) global score of 1 or lower, AND
- •Montreal Cognitive Assessment (MoCA) score of ≥ 18 OR Rey Auditory Verbal Learning Test (RAVLT) >4 words after 30 minutes
- •Capable of giving, and has the capacity to give informed consent
- •Availability of a responsible study partner who can accompany the subject to all planned visits
- •Male or female between 50 and 80 years
- •Normal or clinically acceptable medical history, physical examination, and vital signs
排除标准
- •History of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes).
- •Central nervous system infarct, infection, or focal lesions of clinical significance on MRI scans.
- •Fulfills any contraindication for the use of sirolimus as per the summary of product characteristics, including but not restricted to:
- •Current or planned medication with a strong inhibitor of CYP3A4 or P-gp
- •Current or planned medication with a strong inducer of CYP3A4 or P-gp
- •Other current medications with known serious interaction risks with sirolimus
- •Known allergy or hypersensitivity to sirolimus
- •Significant obesity
- •Untreated and clinically significant hyperlipidemia
- •Treatment with immunosuppressive medications within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted), or chemotherapeutic agents for malignancy within the last 3 years
- •Major surgery within 3 months prior to the planned start of sirolimus treatment, OR has major surgery planned during the period of the trial.
- •Use of experimental medications for Alzheimer's or any other investigational medication or device within 60 days. Participants who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial
研究组 & 干预措施
Rapamycin
Sirolimus tablets will be administered orally, 7 mg once per week during 26 weeks
干预措施: Sirolimus (Drug)
结局指标
主要结局
Change in cerebral glucose metabolism
时间窗: From baseline to six months
Cerebral glucose uptake measured through \[18F\]FDG positron emission tomography
次要结局
- Change in CSF concentration of phosphorylated tau(From baseline to six months)
- Change in CSF concentration of total tau(From baseline to six months)
- Incidence of Treatment-Emergent Adverse Events(From baseline to six months)
- Change in Cerebrospinal fluid (CSF) concentration of amyloid beta 42(From baseline to six months)
- Peak Plasma Concentration (Cmax) of sirolimus(Tested at one occasion between baseline to six months)
- Change in cerebral blood flow(From baseline to six months)
- Area under the concentration versus time curve (AUC) of sirolimus(Tested at one occasion between baseline to six months)
- Trough Plasma Concentration (Cmin) of sirolimus(Tested at one occasion between baseline to six months)
- Change in Montreal Cognitive Assessment (MoCA) rating(From baseline to six months)
研究者
Jonas Svensson
MD
Karolinska Institutet